¹H NMR-Based Biochemometric Analysis of Morus alba Extracts toward a Multipotent Herbal Anti-Infective

Abstract

Mulberry Diels−Alder-type adducts (MDAAs) derived from the white mulberry tree were discovered recently as dual inhibitors of influenza viruses and pneumococci. For the development of a natural product based remedy for respiratory infections, the aim was to (i) identify the most prolific natural source of MDAAs, (ii) develop a protocol to maximize the content of MDAAs in Morus alba extracts, (iii) unravel constituents with the highest anti-infective potential within multicomponent mixtures, and (iv) select and characterize a hit extract as a candidate for further studies. Validated quantitative UPLC-PDA analysis of seven MDAAs (1−7) revealed the root bark as the best starting material and pressurized liquid extraction (PLE) as the optimum technique for extraction. Extracts enriched in MDAAs of a total content above 20% exerted a potent dual anti-influenza virus and antipneumococcal activity. For a detailed analysis of the most bioactive chemical features and molecules within the extracts, 1 H NMR-based heterocovariance analysis (HetCA) was used. According to the multivariate statistical analysis procedure conducted, MDAAs exclusively accounted for the in vitro anti-influenza viral effect. The anti-infective profile of one hit extract (MA60) investigated showed a good tolerance by lung cells (A549, Calu-3) and pronounced in vitro activities against influenza viruses, S. pneumoniae, S. aureus, and inflammation.

Identification of Natural Products Inhibiting SARS-CoV-2 by Targeting Viral Proteases: A Combined in Silico and in Vitro Approach

“…36 This was also confirmed for an MDAAenriched extract (MA60) from mulberry root bark. 36 From an unbiased chemical perspective, which was the starting point for the present in silico-driven, target-based drug discovery study, the obtained results underline the utility of NP virtual screening for the discovery of genuine NPs with high to moderate drug-likeness as novel anti-SARS-CoV-2 scaffolds. From a multitarget and multicomponent perspective, the rich bioactivity profile of the MDAAs derived from previous findings and from this study provide a rationale for the longstanding use of M. alba root bark "sa ̅ ng baí pi ́" in traditional Chinese medicine for the treatment of respiratory infections.…”

“…These new findings further enrich the anti-infective and anti-inflammatory profile of the MDAAs investigated in this study. Previously, it has been shown that they exert (i) a pronounced in vitro anti-inflammatory activity, 36 (ii) an antibacterial activity against Staphylococcus aureus and Streptococcus pneumoniae accompanied by a distinct inhibition of pneumococcal biofilm formation, 45 (iii) an antiviral activity against different influenza virus strains, while (iv) being well tolerated by lung cells (A549, Calu-3). 36 This was also confirmed for an MDAA-enriched extract (MA60) from mulberry root bark.…”

“…Commonly consumed mulberry fruits and other plant parts monographed in the Chinese pharmacopoeia such as leaves and twigs do not contain MDAAs studied in this work in detectable amounts. 36 MDAAs and MDAA-enriched multicomponent extracts of M. alba root bark warrant further studies to evaluate their potential for the treatment of Covid-19 and other acute respiratory infections.…”

“…Thus, MA21 is a hydro-ethanolic extract with a content of 5.4% MDAAs, and MA60 represents an extract optimized toward a high yield of this bioactive compound class (29% MDAAs). 36 For MA60 and MA21, IC 50 values of 23.0 and 38.9 μg/mL were determined, respectively (Figure 1D,E).…”

“…Previously, it has been shown that they exert (i) a pronounced in vitro anti-inflammatory activity, 36 (ii) an antibacterial activity against Staphylococcus aureus and Streptococcus pneumoniae accompanied by a distinct inhibition of pneumococcal biofilm formation, 45 (iii) an antiviral activity against different influenza virus strains, while (iv) being well tolerated by lung cells (A549, Calu-3). 36 This was also confirmed for an MDAAenriched extract (MA60) from mulberry root bark. 36 From an unbiased chemical perspective, which was the starting point for the present in silico-driven, target-based drug discovery study, the obtained results underline the utility of NP virtual screening for the discovery of genuine NPs with high to moderate drug-likeness as novel anti-SARS-CoV-2 scaffolds.…”